The 20 standard amino acids encoded by the Genetic Code were adopted during the RNA World, around 4 billion years ago. This amino acid set could be regarded as a frozen accident, implying that other possible structures could equally well have been chosen to use in proteins. Amino acids were not primarily selected for their ability to support catalysis, since the RNA World already had highly effective cofactors to perform reactions, such as oxidation, reduction and transfer of small molecules. Rather, they were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets...

In developing epithelia, the core planar polarity proteins physically interact with each other and localize asymmetrically at opposite cell ends, forming intercellular complexes that link the polarity of neighboring cells. Using quantitative imaging to examine the composition of the core protein complex in vivo, we find that complex composition is unexpectedly plastic. The transmembrane proteins Frizzled and Flamingo form a stoichiometric nucleus in the complex, while the relative levels of the other four core proteins can vary independently...

In proliferating epithelia of mammalian skin, cells of irregular polygon-like shapes pack into complex, nearly flat two-dimensional structures that are pliable to deformations. In this work, we employ various sensitive correlation functions to quantitatively characterize structural features of evolving packings of epithelial cells across length scales in mouse skin. We find that the pair statistics in direct space (correlation function) and Fourier space (structure factor) of the cell centroids in the early stages of embryonic development show structural directional dependence (statistical anisotropy), which is a reflection of the fact that cells are stretched, which promotes uniaxial growth along the epithelial plane...

Highly pathogenic avian influenza virus H5N1 infects a wide range of host species, with a few cases of sporadic pigeon infections reported in the Middle East and Asia. However, the role of pigeons in the ecology and evolution of H5N1 viruses remains unclear. We previously reported two H5N1 virus strains, isolated from naturally infected pigeons in Egypt, that have several unique mutations in their viral polymerase genes. Here, we investigated the effect of these mutations on H5N1 polymerase activity and viral growth and identified three mutations that affected viral polymerase activity...

Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors...

How can an individual be motivated to perform a target exercise or activity? This question arises in training, therapeutic, and education settings alike, yet despite-or even because of-the large range of extant motivation theories, finding a clear answer to this question can be challenging. Here we propose an application-friendly framework of motivation for a specific activity or exercise that incorporates core concepts from several well-regarded psychological and economic theories of motivation. The key assumption of this framework is that motivation for performing a given activity is determined by the expected benefits and the expected costs of (performance of) the activity...

OBJECTIVE: Accurately segmenting and quantifying brain gliomas from magnetic resonance (MR) images remains a challenging task because of the large spatial and structural variability among brain tumors. To develop a fully automatic and accurate brain tumor segmentation algorithm, we present a probabilistic model of multimodal MR brain tumor segmentation. This model combines sparse representation and the Markov random field (MRF) to solve the spatial and structural variability problem. METHODS: We formulate the tumor segmentation problem as a multi-classification task by labeling each voxel as the maximum posterior probability...

RATIONALE: Chronic lung infections are a hallmark of cystic fibrosis; they are responsible for progressive airway destruction and ultimately lead to respiratory death or the requirement for life-saving bilateral lung transplant. Furthermore, recurrent isolation of airway pathogens such as Pseudomonas aeruginosa in the allograft after transplant is associated with adverse outcomes, including bronchiolitis obliterans syndrome and acute infections. Little information exists on the impact of bilateral lung transplant on the lower-airway microbiota...

We address a long-standing problem concerning the origin of bosonic excitations that strongly interact with charge carriers. We show that the time-resolved pump-probe experiments are capable of distinguishing between regular bosonic degrees of freedom, e.g., phonons, and the hard-core bosons, e.g., magnons. The ability of phonon degrees of freedom to absorb essentially an unlimited amount of energy renders relaxation dynamics nearly independent of the absorbed energy or fluence. In contrast, the hard core effects pose limits on the density of energy stored in the bosonic subsystems resulting in a substantial dependence of the relaxation time on the fluence and/or excitation energy...

The Borromean ^{6}He nucleus is an exotic system characterized by two halo neutrons orbiting around a compact ^{4}He (or α) core, in which the binary subsystems are unbound. The simultaneous reproduction of its small binding energy and extended matter and point-proton radii has been a challenge for ab initio theoretical calculations based on traditional bound-state methods. Using soft nucleon-nucleon interactions based on chiral effective field theory potentials, we show that supplementing the model space with ^{4}He+n+n cluster degrees of freedom largely solves this issue...

We studied the structural effects of point mutations of a membrane protein that cause genetic disease. SLC4A11 is a membrane transport protein (OH(-) /H(+) /NH3 /H2 O) of basolateral corneal endothelium, whose mutations cause some cases of Congenital Hereditary Endothelial Dystrophy and Fuchs Endothelial Corneal Dystrophy. We created a three-dimensional homology model of SLC4A11 membrane domain, using Band 3 (SLC4A1) crystal structure as template. The homology model was assessed in silico and by analysis of mutants designed on the basis of the model...

BACKGROUND: Although effective methods for venous thromboembolism prophylaxis (VTE-P) have been known for decades, reliable implementation has been challenging. OBJECTIVE: Develop reliable VTE-P systems for adult and for pediatric patients to reduce preventable venous thromboembolism (VTE). DESIGN: We used a discovery and diffusion system to first develop an effective system in 1 hospital location, and then spread the principle best practices across the entire 22-hospital system...

BACKGROUND: Hospital-acquired venous thromboembolism (HA-VTE) is a potentially preventable cause of morbidity and mortality. Despite high rates of venous thromboembolism (VTE) prophylaxis in accordance with an institutional guideline, VTE remains the most common hospital-acquired condition in our institution. OBJECTIVE: To improve the safety of all hospitalized patients, examine current VTE prevention practices, identify opportunities for improvement, and decrease rates of HA-VTE...

Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014...

In this work, we describe a very simple approach to develop tailored mesoporosity in any nanostructured heteropolysalt with control over both the mesoporous volume and the pore size. This approach consisting in a treatment of the solid microporous precursor with a basic agent has been tested on the ammonium salt of the Keggin-type [PMo12O40]3- heteropolyanion, and constitutes a novel procedure for the preparation of mesoporous solids with no precedents in the literature. The results obtained in this study allows for extracting two main conclusions: (i) The micro- and mesoporosity structures in the heteropolysalt nanoparticles are independent from each other; and (ii) The development of mesoporosity in the solid material must be related with a process of alkaline degradation within the core of the nanocrystals aggregating into the particles...

We have previously shown that endochondral ossification is finely regulated by the Clock system expressed in chondrocytes during postnatal skeletogenesis. Here we show a sophisticated modulation of bone resorption and bone mass by the Clock system through its expression in bone-forming osteoblasts. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) and Period1 (Per1) were expressed with oscillatory rhythmicity in the bone in vivo, and circadian rhythm was also observed in cultured osteoblasts of Per1::luciferase transgenic mice...